Vesicles within vesicles: what role do multivesicular bodies play in alveolar type II cells?

Abstract

Multivesicular bodies have an unusual struc­ ture when compared with most other types of intracellular organelles. Whereas most or­ ganelles are closed compartments formed by a single cellular membrane, multivesicular bodies consist of numerous small vesicles that are surrounded as a group by another mem­ brane. These organelles are found in most if not all eukaryotic cells. Recent studies have indicated that multivesicular bodies partici­ pate in the metabolism and transport of materials that enter the cells by endocytosis, a general process also likely to be carried out by all cells. lular space into this pathway provides cellu­ lar nutrients, influences cellular metabolism, and may participate in immune responses. The key studies of Goldstein, Brown, and cowork­ ers (3) on receptor-medi ated uptake of low density lipoproteins and the resultant suppres­ sion of cholesterol synthesis, of Cohen and coworkers (5) on endocytosis of epidermal growth factor, of Hubbard (6) on hepatic me­ tabolism of asialoglycoproteins, and of many other researchers illustrate the general func­ tional roles of multivesicula r bodies. These general concepts can be summarized as follows. Receptor molecules reside on a cell surface, scattered randomly or clustered to­ gether, with their ligand-binding moieties ex­ posed to the extracellular space. When ligands bind to the receptor, the complex, or some­ times receptors alone, enter the cell in small vesicles, which may be clathrin-coated (7-9). These vesicles fuse or enlarge to become an endosome, an acidic compartment that gener­ ally lacks internal vesicles. If the internalized receptors are to be recycled to the cell sur­ face, they cluster together and bud off from the endosome to form a vesicle (10), which fuses with the plasma membrane. This pro­ cess reexposes the ligand-binding site of the receptor to the extracellular space. During or after the receptors are shed, if this occurs, small vesicles appear within the lumen of the endosome, and the organelle is now appropri­ ately called a multivesicular endosome. As used by Wall and Hubbard (9), this term aptly describes both the lack of lysosomal enzymes, which is characteristic of endosomes, and the organellar structure. Within a few minutes af­ ter endocytosis has begun, these large, pale- staining, multivesicular endosomes contain the internalized ligand. Most studies suggest that the inner vesicles appear prior to the en­